The Undruggable Enemy: Why This Tiny Vaccine is Making Cancer Cells Sweat (And Investors Cheer)

In the ongoing war against cancer, some enemies are famously difficult to hit. One such stubborn target is a mutated protein known as KRAS (mutant-Kirsten rat sarcoma), which plays a significant role in the pathology of disease. For decades, developing therapies to target KRAS has been extraordinarily challenging, primarily because the protein lacks readily available binding pockets and holds a strong affinity to an activating molecule called guanosine triphosphate (GTP). The inability to effectively "drug" KRAS has long been a major hurdle, as these mutations are estimated to be present in roughly one-third of all cancers, contributing strongly to poor patient outcomes.

However, the tide may be turning, thanks to promising new approaches, particularly those involving immunotherapy and vaccines. Elicio Therapeutics has recently garnered significant attention with positive results from its novel cancer vaccine, ELI-002. The data from the extended Phase I AMPLIFY-201 trial (NCT04853017) suggests that ELI-002 is not just a marginal improvement, but a potentially transformative tool in the fight against hard-to-treat solid tumors.

A Closer Look at the Trial’s Stunning Results

The Phase I AMPLIFY-201 trial focused on patients suffering from two aggressive cancers: pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer. These indications are often associated with extremely poor outcomes upon diagnosis. The results revealed that the mKRAS-targeting jab was associated with dramatic survival benefits.

Specifically, the ELI-002 vaccine was found to reduce the risk of death by 77% in these patients. Furthermore, the vaccine drastically lowered the risk of cancer relapse by an impressive 88%. These results were strong enough to warrant publication in the prestigious journal Nature Medicine.

The efficacy of the treatment translated into significant increases in the amount of time patients remained cancer-free and alive. At the extended follow-up cut-off for the trial, the median relapse-free survival (mRFS)—which measures the time patients live without the cancer returning—reached 16.33 months. Even more encouraging, the overall survival (OS) of treated patients reached 28.94 months.

Beyond survival metrics, the vaccine also showed clear activity at the cellular level. Tumor biomarker responses were observed in 84% of the patients treated. Crucially, 24% of patients achieved complete biomarker clearance. This means that for nearly a quarter of the patients, the signs of the disease that doctors look for had completely disappeared.

How ELI-002 Teaches the Body to Fight

ELI-002 is a peptide cancer vaccine designed to activate the body’s own defense mechanisms. Unlike traditional chemotherapy, which broadly attacks dividing cells, this vaccine aims to teach the immune system to specifically recognize and destroy the rogue cancer cells.

The vaccine achieves this by consisting of two key components: a KRAS peptide antigen and an immune-stimulatory oligonucleotide. Think of the KRAS peptide antigen as a “Most Wanted” poster for the cancer cell. It shows the immune system exactly what the mutated KRAS protein looks like. The immune-stimulatory oligonucleotide acts like a siren or alarm, telling the immune system to pay close attention.

The entire treatment is delivered through Elicio’s specialized Amphiphile (AMP) platform. This platform is crucial because it ensures that the vaccine components are transported directly to the lymph nodes. The lymph nodes are essentially the body’s training centers for immune cells. Once there, the vaccine activates and amplifies the activity of the adaptive immune system—the sophisticated part of the immune system responsible for generating specific, targeted attacks. This process encourages T-cells (key immune cells) to identify and destroy cancer cells expressing the specific mKRAS antigens.

The connection between the immune response and patient benefit was crystal clear in the trial data. The patients who gained the greatest therapeutic benefit from ELI-002 were those who demonstrated strong, specific T-cell responses against mKRAS that exceeded a certain antitumour efficacy threshold. Tellingly, these highly responsive patients had not yet reached the median relapse-free survival or overall survival endpoints during the follow-up period, suggesting that the immune responses initiated by the jab are both significant and durable. Due to this mechanism, ELI-002 has shown potential applicability across a range of solid tumor indications.

Financial and Regulatory Impact

Promising clinical data often reverberates immediately in the financial markets, and Elicio’s announcement was no exception. Following the news, Elicio’s stock value saw a rapid increase of 14.8%, jumping from $8.65 at the close of the market on August 11th to $9.93 when the market opened the very next day, August 12th.

Despite the excitement surrounding ELI-002, the field of KRAS-targeting therapies is heating up. There are other promising therapies currently in late-stage trials. For instance, Revolution Medicines’ GTP-bound KRAS G12 inhibitor, known as daraxonrasib, has already made significant strides. Daraxonrasib received the coveted breakthrough therapy designation from the US Food and Drug Administration (FDA) for use in PDAC in June 2025. Revolution Medicines has stated its goal to complete enrollment for its Phase III RASolute 302 trial (NCT06625320) by the end of the year. If this drug is approved, GlobalData forecasts that it will achieve blockbuster status by 2029, eventually raking in $2.1 billion by 2031.

The Vaccine Modality Crossroads: Non-mRNA vs. mRNA

Elicio’s ELI-002 represents a non-mRNA vaccine approach. This stands in contrast to the rapid development of mRNA-based cancer vaccines.

The mRNA vaccine modality has also shown significant promise in early-stage trials. For example, BioNTech and Genentech developed a candidate called autogene cevumeran, which elicited durable CD8 immune responses in PDAC when used alongside the PDL-1 inhibitor Tecentriq (atezolizumab) as an adjuvant (a therapy given after the primary treatment). These companies have already moved autogene cevumeran into Phase II trials where it is being investigated as an adjuvant to standard of care (SoC) chemotherapy. The results from their colorectal cancer trial are anticipated to be available in late 2025 or early 2026.

However, the future regulatory and financial landscape for mRNA vaccines faces a potential complication. US Health Secretary Robert F Kennedy Jr (RFK Jr) has publicly called for a reduction in funding for 22 mRNA vaccine projects. If this funding cut materializes, it could potentially slow the progression of pipelines within the mRNA sector and restrict opportunities for development in this specific modality.

This potential shift could inadvertently create a significant market opportunity for non-mRNA based vaccines like ELI-002. A restriction in mRNA funding could give ELI-002 a better chance at securing its own clinical-stage development funding, and potentially provide it with a valuable head start in the market if it gains regulatory approval first. That said, the actual impact of RFK Jr’s decision on the market remains unclear at this time.

Looking Ahead

Elicio’s ELI-002 is currently continuing its development path and is also being investigated in the Phase II AMPLIFY-7P trial (NCT05726864). The strong Phase I data has suggested that this approach, which directly targets mKRAS and utilizes the AMP platform to train the adaptive immune system in the lymph nodes, holds significant promise for patients dealing with cancers traditionally resistant to treatment. As research continues into both peptide and mRNA vaccines, and as small molecule inhibitors like daraxonrasib advance through late-stage trials, the era of the "undruggable" KRAS mutation may finally be drawing to a close.

Cancer Researchers:

1. Dr. Kit Lam

• Dr. Lam is a Distinguished Professor at the University of California, Davis (UC Davis) in the Department of Biochemistry and Molecular Medicine.

• His research focuses on developing peptide nanoparticles to diagnose and treat cancer.

• He is co-founder of T-NanoBio Therapeutics, a biotechnology startup aiming to commercialize nano immune-engagers built from peptides to promote anti-tumor responses. 

2. Dr. Hadiyah-Nicole Green

• Dr. Green is an interdisciplinary cancer researcher and the founder of the Ora Lee Smith Cancer Research Foundation.

• She developed a patented, targeted cancer treatment using nanoparticles and a laser, which has shown promise in animal studies.

• Her work aims to provide minimally invasive and effective cancer treatment options, with an emphasis on equitable access to care. 

3. Dr. Zihua Wang

• Dr. Wang is a Research Assistant Professor at Cold Spring Harbor Laboratory.

• His research focuses on developing new molecular genetic technologies for cancer studies, including early detection and prognosis.

• While his work is not solely based on peptides, he has developed several techniques for analyzing cancer tumor profiles, with a focus on applying next-generation sequencing to detect rare mutations and other variants in cancer.